The Effect of Surgical Procedure in the Nasal Cavity on the Passive Avoidance Conditioning and the Hypothalamic Level of Monoamines in Rats.

A rat biological model of septoplasty was used to study the effect of surgery on passive avoidance conditioning (PAC). Septoplasty was shown to increase anxiety and to reduce exploratory activity in rodents during PAC. A neurochemical analysis of the hypothalamus was carried out immediately after the end of the experiment and showed an increase in norepinephrine (NE) metabolism after septoplasty. The finding was tentatively associated with activation of the hypothalamic-pituitary-adrenal axis.

Molecular Evidence for Olfactory Neuroblastoma as a Tumor of Malignant Globose Basal Cells.

Olfactory neuroblastoma (ONB, esthesioneuroblastoma) is a sinonasal cancer with an underdeveloped diagnostic toolkit, and is the subject of many incidents of tumor misclassification throughout the literature. Despite its name, connections between the cancer and normal cells of the olfactory epithelium have not been systematically explored and markers of olfactory epithelial cell types are not deployed in clinical practice. Here, we utilize an integrated human-mouse single-cell atlas of the nasal mucosa, including the olfactory epithelium, to identify transcriptomic programs that link ONB to a specific population of stem/progenitor cells known as olfactory epithelial globose basal cells (GBCs). Expression of a GBC transcription factor NEUROD1 distinguishes both low- and high-grade ONB from sinonasal undifferentiated carcinoma, a potential histologic mimic with a distinctly unfavorable prognosis. Furthermore, we identify a reproducible subpopulation of highly proliferative ONB cells expressing the GBC stemness marker EZH2, suggesting that EZH2 inhibition may play a role in the targeted treatment of ONB. Finally, we study the cellular states comprising ONB parenchyma using single-cell transcriptomics and identify evidence of a conserved GBC transcriptional regulatory circuit that governs divergent neuronal-versus-sustentacular differentiation. These results link ONB to a specific cell type for the first time and identify conserved developmental pathways within ONB that inform diagnostic, prognostic, and mechanistic investigation.

18F-fluorodeoxyglucose positron emission tomography findings of peripheral nerve sheath tumour of the nasal cavity in a dog.

An 8-year-old Miniature Poodle presented with chronic sneezing and unilateral epistaxis. A left-sided intranasal mass was identified on computed tomography. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) was performed to evaluate the metabolic activity of the mass. The intranasal mass showed mildly increased 18F-FDG uptake. The maximal and mean standardized uptake values (SUVs) of the mass were 3.4 and 2.6, respectively. The maximal SUV of the mass/mean SUV of the normal liver was 2.5. The 7-cm soft, pink mass was easily removed through rhinoscopy, with subsequent dramatic improvement in clinical signs. Histopathological and immunohistochemical analyses determined that the mass was an intermediate-grade malignant peripheral nerve sheath tumour (PNST). This is the first report of 18F-FDG PET findings in a PNST in dogs.

Prognostic significance of PD-1, CTLA-4, CD4, and CD8 expression in olfactory neuroblastoma.

There are limited data regarding immune surveillance mechanisms in olfactory neuroblastoma. We investigated the expression of programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), CD4, and CD8 in olfactory neuroblastoma to identify potential therapeutic targets. Immunohistochemistry was used to detect PD-1 and CTLA-4 and measure the numbers of CD4+ and CD8+ T cells in 56 patients with olfactory neuroblastoma. The relationships between these molecules in tumor microenvironment, clinicopathological features, and survival were analyzed. The prevalence of PD-1 in Kadish C stage was 24.14%, significantly greater than in Kadish A and B stage. CD4+ T-cell and CD8+ T-cell levels correlated with higher Hyams histological grade and Kadish stage. In addition, PD-1 was related positively with CTLA-4, CD4+ T cells, and CD8+ T cells in olfactory neuroblastoma. Univariate survival analysis showed that higher PD-1 positivity, CD8+ T cells, and Hyams grade correlated with worse clinical outcome. Multivariate analysis showed that the expression of PD-1 was an independent parameter for poor prognosis. In conclusion, olfactory neuroblastoma with PD-1 expression had more aggressive clinicopathological features and worse prognosis. PD-1 may potentially predict the outcome of olfactory neuroblastoma patients.

The prognostic value of S-100 protein and Ki-67 index in olfactory neuroblastoma.

OBJECTIVE: To evaluate the prognostic value of S-100 protein and Ki-67 labeling index in olfactory neuroblastomas. METHODS: A retrospective study was conducted on a cohort of 85 patients with olfactory neuroblastomas. The immunohistochemical expression of S-100 and Ki-67 was assessed, and the predictive value of S-100 and Ki-67 was further evaluated. The optimal cutoff value of Ki-67 labeling index was determined using time-dependent receiver operating characteristic curve analysis. Overall survival and progression-free survival were assessed using the Kaplan-Meier method. RESULTS: A cut-off Ki-67 labeling index value of 67.5% was determined for prognosis in patients with olfactory neuroblastomas. There was a significant correlation between Ki-67 expression and cervical lymph node metastasis (P = 0.049). Compared with S-100 (+), S-100 (-) was associated with a higher rate of lymph node metastasis and a higher level of Ki-67 (P = 0.007, < 0.001, respectively), as well as an advanced Kadish stage (P = 0.037). Survival analyses showed that patients with S-100 (+) had better 5-year overall survival than those with S-100 (-) (P = 0.028), and patients with both S-100 (+) and Ki-67 (<67.5%) had superior 5-year overall survival compared with all the other patients (P = 0.0225). CONCLUSION: Our findings suggest that S-100 combined with Ki-67 labeling index are reliable prognostic factors in patients with olfactory neuroblastomas.

[IgG4-related disease in nasal cavity and paranasal sinuses: a clinicopathological analysis of ten cases].

Objective: To study clinicopathological features and differential diagnosis of IgG4-related diseases (IgG4-RD) in nasal cavity and paranasal sinuses. Methods: A retrospective analysis was performed in patients presenting initially with rhinosinusitis or a nasal mass, who also underwent nasal mucosa biopsy in Beijing Tongren Hospital Affiliated to Capital Medical University, from March 2016 to March 2021. According to the latest international classification diagnostic criteria of IgG4-RD published by the American Society of Rheumatology (ACR)/European Association for Rheumatology (EULAR) in 2019, 10 cases of nasal cavity and paranasal sinuses IgG4-RD were diagnosed and included in the study. The clinical features, histopathology and immunohistochemical expression of IgG and IgG4 were analyzed. Results: Among the 10 patients, five patients were male and five female. The age ranged from 30 to 71 years (median 52.7 years). Nasal polyp/nasal masses were seen in six cases, and lacrimal gland swelling was found in four cases. The serum IgG and IgG4 level was increased in four cases. Microscopically, all 10 cases showed intense lymphoplasmocytic infiltration and varying degrees of fibrosis in nasal or sinus mucosa, while four cases showed occlusive vasculitis. The number of IgG4 positive plasma cells in nasal mucosa was more than 10/high power field (HPF), with a mean of 67/HPF. The number of IgG4 positive plasma cells in the cases with severe fibrosis was significantly lower than in those without. The ratio of IgG4+/IgG+plasma cells was higher than 40% in six cases. Conclusions: IgG4-RD in nasal cavity and paranasal sinuses is a local manifestation of a systemic disease, while nasal cavity and paranasal sinuses are rarely involved by IgG4-RD. The diagnosis is based on clinical symptoms, imaging, IgG4-related serology and histopathologic scores. Histopathology has a core diagnostic value. IgG4 serology and imaging have important diagnostic values in the cases without biopsy.

Prognostic value of microvessel density and its correlation with clinicopathological features in human olfactory neuroblastoma.

Although angiogenesis plays an important role in tumor growth and invasion, its role in the progression of olfactory neuroblastoma (ONB) has rarely been published. The aim of the present research was to analyze the prognostic role of microvessel density (MVD) in ONB and its association with clinicopathological parameters. 70 ONB cases were assessed for immunohistochemical expression of CD31, CD34, CD105, VEGF, and VEGFR2. The expression of CD105-MVD was negatively associated with histological grade and tumor Kadish stage, and its expression was positively correlated with the expression of VEGF/VEGFR2. Low expression of CD105-MVD and high tumor histological grade were strongly associated with poor survival. Thus, CD105-MVD was demonstrated to be a valuable independent prognostic indicator for ONB. MVD is expected to be useful as an important marker to distinguish tumor histological grade.

Clinical outcomes, Kadish-INSICA staging and therapeutic targeting of somatostatin receptor 2 in olfactory neuroblastoma.

INTRODUCTION: Olfactory neuroblastoma (ONB) is a rare cancer of the sinonasal region. We provide a comprehensive analysis of this malignancy with molecular and clinical trial data on a subset of our cohort to report on the potential efficacy of somatostatin receptor 2 (SSTR2)-targeting imaging and therapy. METHODS: We conducted a retrospective analysis of 404 primary, locally recurrent, and metastatic olfactory neuroblastoma (ONB) patients from 12 institutions in the United States of America, United Kingdom and Europe. Clinicopathological characteristics and treatment approach were evaluated. SSTR2 expression, SSTR2-targeted imaging and the efficacy of peptide receptor radionuclide therapy [PRRT](177Lu-DOTATATE) were reported in a subset of our cohort (LUTHREE trial; NCT03454763). RESULTS: Dural infiltration at presentation was a significant predictor of overall survival (OS) and disease-free survival (DFS) in primary cases (n = 278). Kadish-Morita staging and Dulguerov T-stage both had limitations regarding their prognostic value. Multivariable survival analysis demonstrated improved outcomes with lower stage and receipt of adjuvant radiotherapy. Prophylactic neck irradiation significantly reduces the rate of nodal recurrence. 82.4% of the cohort were positive for SSTR2; treatment of three metastatic cases with SSTR2-targeted peptide-radionuclide receptor therapy (PRRT) in the LUTHREE trial was well-tolerated and resulted in stable disease (SD). CONCLUSIONS: This study presents pertinent clinical data from the largest dataset, to date, on ONB. We identify key prognostic markers and integrate these into an updated staging system, highlight the importance of adjuvant radiotherapy across all disease stages, the utility of prophylactic neck irradiation and the potential efficacy of targeting SSTR2 to manage disease.

Transplantation of Human Induced Pluripotent Stem Cell-Derived Airway Cells on Vitrigel Membrane into Rat Nasal Cavity.

The nasal mucosa functions as a frontline biological defense against various foreign substances and pathogens. Maintaining homeostasis of the nasal epithelium is necessary to promote good health. Nasal epithelia are constantly replaced under normal conditions. However, hereditary diseases, including primary ciliary dyskinesia and cystic fibrosis, can result in intractable dysfunction of the nasal mucosa. Since there is no treatment for this underlying condition, extrinsic manipulation is necessary to recover and maintain nasal epithelia in cases of hereditary diseases. In this study, we explored the use of airway epithelial cells (AECs), including multiciliated airway cells, derived from human induced pluripotent stem cells (iPSCs) on porcine atelocollagen vitrigel membranes, as a candidate of a therapeutic method for irreversible nasal epithelial disorders. To confirm the regenerative capacity of iPSC-derived AECs, we transplanted them into nasal cavities of nude rats. Although the transplanted cells were found within cysts isolated from the recipient nasal respiratory epithelia, they survived in some rats. Furthermore, the surviving cells were composed of multiple cell types similar to the human airway epithelia. The results could contribute to the development of novel transplantation-related technologies for the treatment of severe irreversible nasal epithelial disorders. Impact Statement Nasal respiratory epithelia are important for the functions of nasal cavity, including humidifying the air and filtering various toxic substances. However, hereditary diseases, including primary ciliary dyskinesia and cystic fibrosis, can result in intractable dysfunction of the nasal mucosa. Our novel method to transplant airway epithelial cells derived from human induced pluripotent stem cells will be a candidate method to replace malfunctioned nasal respiratory epithelia in such a situation. To secure our method's safety, we used porcine atelocollagen vitrigel membranes, which prevent the immune response and bovine spongiform encephalopathy, as a scaffold.

Determinants of SARS-CoV-2 entry and replication in airway mucosal tissue and susceptibility in smokers.

Understanding viral tropism is an essential step toward reducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, decreasing mortality from coronavirus disease 2019 (COVID-19) and limiting opportunities for mutant strains to arise. Currently, little is known about the extent to which distinct tissue sites in the human head and neck region and proximal respiratory tract selectively permit SARS-CoV-2 infection and replication. In this translational study, we discover key variabilities in expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), essential SARS-CoV-2 entry factors, among the mucosal tissues of the human proximal airways. We show that SARS-CoV-2 infection is present in all examined head and neck tissues, with a notable tropism for the nasal cavity and tracheal mucosa. Finally, we uncover an association between smoking and higher SARS-CoV-2 viral infection in the human proximal airway, which may explain the increased susceptibility of smokers to developing severe COVID-19. This is at least partially explained by differences in interferon (IFN)-ß1 levels between smokers and non-smokers.

Metabolic Reprogramming of Nasal Airway Epithelial Cells Following Infant Respiratory Syncytial Virus Infection.

Respiratory syncytial virus (RSV) is a seasonal mucosal pathogen that infects the ciliated respiratory epithelium and results in the most severe morbidity in the first six months of life. RSV is a common cause of acute respiratory infection during infancy and is an important early-life risk factor strongly associated with asthma development. While this association has been repeatedly demonstrated, limited progress has been made on the mechanistic understanding in humans of the contribution of infant RSV infection to airway epithelial dysfunction. An active infection of epithelial cells with RSV in vitro results in heightened central metabolism and overall hypermetabolic state; however, little is known about whether natural infection with RSV in vivo results in lasting metabolic reprogramming of the airway epithelium in infancy. To address this gap, we performed functional metabolomics, 13C glucose metabolic flux analysis, and RNA-seq gene expression analysis of nasal airway epithelial cells (NAECs) sampled from infants between 2-3 years of age, with RSV infection or not during the first year of life. We found that RSV infection in infancy was associated with lasting epithelial metabolic reprogramming, which was characterized by (1) significant increase in glucose uptake and differential utilization of glucose by epithelium; (2) altered preferences for metabolism of several carbon and energy sources; and (3) significant sexual dimorphism in metabolic parameters, with RSV-induced metabolic changes most pronounced in male epithelium. In summary, our study supports the proposed phenomenon of metabolic reprogramming of epithelial cells associated with RSV infection in infancy and opens exciting new venues for pursuing mechanisms of RSV-induced epithelial barrier dysfunction in early life.

New insights into structure and function of bis-phosphinic acid derivatives and implications for CFTR modulation.

C407 is a compound that corrects the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein carrying the p.Phe508del (F508del) mutation. We investigated the corrector effect of c407 and its derivatives on F508del-CFTR protein. Molecular docking and dynamics simulations combined with site-directed mutagenesis suggested that c407 stabilizes the F508del-Nucleotide Binding Domain 1 (NBD1) during the co-translational folding process by occupying the position of the p.Phe1068 side chain located at the fourth intracellular loop (ICL4). After CFTR domains assembly, c407 occupies the position of the missing p.Phe508 side chain. C407 alone or in combination with the F508del-CFTR corrector VX-809, increased CFTR activity in cell lines but not in primary respiratory cells carrying the F508del mutation. A structure-based approach resulted in the synthesis of an extended c407 analog G1, designed to improve the interaction with ICL4. G1 significantly increased CFTR activity and response to VX-809 in primary nasal cells of F508del homozygous patients. Our data demonstrate that in-silico optimized c407 derivative G1 acts by a mechanism different from the reference VX-809 corrector and provide insights into its possible molecular mode of action. These results pave the way for novel strategies aiming to optimize the flawed ICL4-NBD1 interface.

Exploring Pleiotropic Functions of Canine ß-Defensin 103: Nasal Cavity Expression, Antimicrobial Activity, and Melanocortin Receptor Activity.

Canine ß-defensin 103 (cBD103) and its common variant cBD103ΔG23 are multitasking polypeptides. As a ß-defensin, cBD103 is one of many antimicrobial agents used by the innate immunity to thwart pathogenic colonization. In this study, we showed that cBD103 was expressed throughout the nasal cavity, with primary expression in the nares as well as respiratory and olfactory epithelia. In the rostral nasal concha, cBD103 was expressed in the epithelium, and to a lesser degree in the lamina propria, but was absent in goblet cells. In the main olfactory epithelium, virtually all cells in the epithelial layer and select cells associated with Bowman's glands expressed cBD103. We also showed that the ΔG23 mutation did not appreciably alter the antimicrobial activity of the peptide against several species of microorganisms tested in nutrient-rich or minimal media or minimal media with salt added. Moreover, we showed antimicrobial activity in minimal media did not necessarily predict the inhibitory action of the peptide in nutrient-rich media. Both forms of cBD103 caused ultrastructural changes (membrane blebbing, condensation of intracellular contents and cell wall lysis) in Escherichia coli and Staphylococcus aureus. As a ligand of the melanocortin receptors, we showed that cBD103ΔG23 increased ERK1/2 activation and cAMP accumulation when bound to the human or canine melanocortin-4 receptor, acting as a weak allosteric agonist.

Impact of Draf III, Draf IIb, and Draf IIa frontal sinus surgery on nasal irrigation distribution.

BACKGROUND: Delivery of topical pharmacotherapy to the paranasal sinuses remains integral to the management of chronic rhinosinusitis. The frontal sinus remains a difficult access site for irrigations, often limited by its position relative to the nostril and ethmoid sinus. In view of the previous demonstration of improved frontal sinus irrigation with Draf III vs Draf IIa, in this work we sought to evaluate topical access of Draf IIb relative to Draf IIa and Draf III modification of the frontal sinus outflow tract. METHODS: Unfixed human cadaver heads were dissected using Draf IIa, Draf IIb, and Draf III frontal sinusotomies. Draf IIa, Draf IIb, and Draf III frontal sinusotomies were performed in progressive sequence on each cadaver head. Nasal irrigation fluid access to the frontal sinus was tested after each successive frontal sinus intervention. Irrigations were performed using Frankfort horizontal and vertex positioning. Blinded reviewers were then asked to evaluate nasal irrigation access based on an ordinal scale. RESULTS: Eight cadaveric specimens (age, 78 ± 12.3 years; 62.5% female) were assessed. The greatest distribution scores were recorded by Draf III, then IIb, and then IIa (90.7% vs 81.3% vs 50.1%; p < 0.001). Similarly, the rate of lavage was greatest with Draf III (50% vs 12.5% vs 12.5%). Vertex positioning and increasing volume trended toward improved distribution but did not reach statistical significance. CONCLUSION: Adequate delivery of topical therapy to the paranasal sinuses by nasal irrigation remains critical in the postoperative state. Although increasing the dimensions of the frontal recess improves nasal irrigation delivery, the Draf III procedure provides the optimal delivery of pharmacotherapy in those with frontal sinus disease.

Intranasal Nanoparticulate Systems as Alternative Route of Drug Delivery.

There is always a need for alternative and efficient methods of drug delivery. The nasal cavity can be considered as a non-invasive and efficient route of administration. It has been used for local, systemic, brain targeting, and vaccination delivery. Although many intranasal products are currently available on the market, the majority is used for local delivery with fewer products available for the other targets. As nanotechnology utilization in drug delivery has rapidly spread out, the nasal delivery has become attractive as a promising approach. Nanoparticulate systems facilitate drug transportation across the mucosal barrier, protect the drug from nasal enzyme degradation, enhance the delivery of vaccines to the lymphoid tissue of the nasal cavity with an adjuvant activity, and offer a way for peptide delivery into the brain and the systemic circulation, in addition to their potential for brain tumor treatment. This review article aims at discussing the potential benefit of the intranasal nanoparticulate systems, including nanosuspensions, lipid and surfactant, and polymer-based nanoparticles as regards productive intranasal delivery. The aim of this review is to focus on the topicalities of nanotechnology applications for intranasal delivery of local, systemic, brain, and vaccination purposes during the last decade, referring to the factors affecting delivery, regulatory aspects, and patient expectations. This review further identifies the benefits of applying the Quality by Design approaches (QbD) in product development. According to the reported studies on nanotechnology-based intranasal delivery, potential attention has been focused on brain targeting and vaccine delivery with promising outcomes. Despite the significant research effort in this field, nanoparticle-based products for intranasal delivery are not available. Thus, further efforts are required to promote the introduction of intranasal nanoparticulate products that can meet the requirements of regulatory affairs with high patient acceptance.

Nasal Cavity Administration of Melanin-Concentrating Hormone Improves Memory Impairment in Memory-Impaired and Alzheimer's Disease Mouse Models.

Melanin-concentrating hormone (MCH) is a highly conserved neuropeptide known to exhibit important functions in the brain. Some studies have reported that MCH improves memory by promoting memory retention. However, the precise molecular mechanisms by which MCH enhances memory impairment have yet to be fully elucidated. In this study, MCH was administered to the scopolamine-induced memory-impaired mice via the nasal cavity to examine the acute effects of MCH and Alzheimer's disease (AD) mouse models to evaluate the chronic effects of MCH. MCH improved memory impairment in both models and reduced soluble amyloid beta in the cerebral cortex of APP/PS1 transgenic mice. In vitro assays also showed that MCH inhibits amyloid beta-induced cytotoxicity. Furthermore, MCH increased long-term potentiation (LTP) in the hippocampus of wild-type and 5XFAD AD mouse model. To further elucidate the mechanisms of the chronic effect of MCH, the levels of phosphorylated CREB and GSK3ß, and the expression of BDNF, TrkB and PSD95 were examined in the cerebral cortex and hippocampus. Our findings indicate that MCH might have neuroprotective effects via downstream pathways associated with the enhancement of neuronal synapses and LTP. This suggests a therapeutic potential of MCH for the treatment of neurodegenerative diseases such as AD.

Nose-to-Brain Delivery.

The global prevalence of neurologic disorders is rising, and yet we are still unable to deliver most drug molecules, in therapeutic quantities, to the brain. The blood brain barrier consists of a tight layer of endothelial cells surrounded by astrocyte foot processes, and these anatomic features constitute a significant barrier to drug transport from the blood to the brain. One way to bypass the blood brain barrier and thus treat diseases of the brain is to use the nasal route of administration and deposit drugs at the olfactory region of the nares, from where they travel to the brain via mechanisms that are still not clearly understood, with travel across nerve fibers and travel via a perivascular pathway both being hypothesized. The nose-to-brain route has been demonstrated repeatedly in preclinical models, with both solution and particulate formulations. The nose-to-brain route has also been demonstrated in human studies with solution and particle formulations. The entry of device manufacturers into the arena will enable the benefits of this delivery route to become translated into approved products. The key factors that determine the efficacy of delivery via this route include the following: delivery to the olfactory area of the nares as opposed to the respiratory region, a longer retention time at the nasal mucosal surface, penetration enhancement of the active through the nasal epithelia, and a reduction in drug metabolism in the nasal cavity. Indications where nose-to-brain products are likely to emerge first include the following: neurodegeneration, post-traumatic stress disorder, pain, and glioblastoma.

The theory of a "staphylococcus superantigen" in chronic rhinosinusitis with nasal polyps: myth or reality?

OBJECTIVE: The aim of our study was to search for evidence of a "staphylococcus superantigen" in chronic rhinosinusitis with nasal polyps. PATIENTS AND METHODS: Sixty-nine patients with chronic rhinosinusitis with nasal polyps and 45 healthy controls were included in the study. All patients in the study and control groups underwent bacteriological and immunological examination on nasal smear samples. Total IgE and the following cytokines were tested in all patients: tumor necrosis factor (TNF), interleukin-1 (IL1), interleukin-6 (IL6), interleukin-8 (IL8). RESULTS: The concentration of bacteria in the nasal cavity was much higher in patients in the study group compared to those in the control group, mainly due to staphylococci. In species identification of staphylococci, bacteria most represented were S. aureus and S. epidermidis. The greater the concentration of S. aureus, the lower the level of IgE. Proinflammatory cytokines were uniformly increased in patients with nasal polyps. The level of IgE was maximal in patients with chronic rhinosinusitis with nasal polyps with a poor growth of culture and minimal in patients with abundant growth, suggesting that in the latter the effect of eosinophilic inflammation on the disease was reduced, and conversely, the activity of eosinophilic inflammation was maximal with a poor seeding of the nasal cavity. CONCLUSIONS: Although this study has some limits, our findings do not support the theory of a staphylococcus superantigen in which the IgE level and eosinophilic inflammation should increase with increasing activity of Staphylococcus aureus. Further research supported by a larger sample of patients is required to better delineate the role of a staphylococcus superantigen in the pathogenesis of patients with chronic rhinosinusitis with nasal polyps.

Measurement of fractional exhaled nitric oxide and nasal nitric oxide in male patients with obstructive sleep apnea.

OBJECTIVE: Airway inflammation plays an important role in obstructive sleep apnea (OSA); exhaled nitric oxide is regarded as a noninvasive marker of airway inflammation. The aim of this study was to evaluate fractional exhaled nitric oxide (FeNO) and nasal nitric oxide (nNO) in patients with OSA. METHODS: Seventy-five patients with OSA and 30 health controls were enrolled in this study. FeNO and nNO were measured before and after sleep. Nasal lavage was performed in 31 non-smoking individuals immediately after NO measurement in the morning. The sample of nasal lavage was taken for cell classification and analyzing interleukin 6 (IL-6) and interleukin 8 (IL-8). RESULTS: Both FeNO and nNO were significantly higher in OSA (before sleep FeNO 21.08 ± 8.79 ppb vs.16.90 ± 6.86 ppb, p = 0.022; after sleep FeNO 25.57 ± 15.58 ppb vs.18.07 ± 6.25 ppb, p = 0.003; before sleep nNO 487.03 ± 115.83 ppb vs. 413.37 ± 73.10 ppb, p = 0.001; after sleep nNO 550.07 ± 130.24 ppb vs. 460.43 ± 109.77 ppb, p < 0.001). Furthermore, in non-smoking OSA, nNO levels were positively correlated with apnea hypopnea index (AHI) and average decrease of pulse arterial oxygen saturation (SpO2); after sleep, nNO was also positively associated to recording time with SpO2 < 90% and negatively associated to minimum SpO2. Both before and after sleep nNO levels were positively correlated with the percentage of neutrophils in nasal lavage (r = 0.528, p = 0.014; r = 0.702, p < 0.001, respectively). Additionally, before sleep nNO was also positively associated with IL-6 (r = 0.586, p = 0.005) and IL-8 (r = 0.520, p = 0.016) concentration. CONCLUSION: This study sustains the presence of airway inflammation in OSA patients with the increase of FeNO and nNO. The data suggests nNO might have greater value than FeNO since it positively correlated with OSA severity, and nNO is a potential bio-marker of nasal inflammation in non-smoking OSA patients.

The amendatory effect of hesperidin and thymol in allergic rhinitis: an ovalbumin-induced rat model.

PURPOSE: Allergic rhinitis is an immunoglobulin-E (Ig-E)-mediated response driven by type 2 helper T cells. Hesperidin and thymol are biological agents that possess antioxidant and anti-inflammatory characteristics. The purpose of this study was to investigate the effects of hesperidin and thymol in rats with ovalbumin-induced allergic rhinitis. METHODS: Thirty adult Sprague-Dawley rats were randomly assigned into five groups, each containing six animals. The first group constituted the negative control group, while the remaining groups were exposed to an ovalbumin-induced model of allergic rhinitis. In the provocation stage, 4 mL/kg saline was administered to the positive control group, 10 mg/kg desloratadine to the reference group, 100 mg/kg hesperidin to the hesperidin group, and 20 mg/kg thymol to the thymol group, all by gastric lavage for 7 days. Nasal symptoms were scored on day 22. Rats were then sacrificed, and intracardiac blood specimens were collected to measure plasma total Ig-E, IL-5, IL-13, total antioxidant capacity (TAC), and total oxidant status (TOS) levels. Nasal tissues were extracted for histopathological and immunochemical examination. RESULTS: Nasal symptom scores were highest in the positive control group, while hesperidin and thymol ameliorated these symptoms to the same extent as desloratadine. Ig-E, IL-5, IL-13, and TOS levels increased, while TAC levels decreased significantly in the allergic rhinitis group compared to the other groups. Significant improvement in these parameters was observed in both the hesperidin and thymol groups. At histopathological and immunohistochemical examination of the nasal cavity, severe allergic inflammation and severe TNF-α expression was determined in rats from the allergic rhinitis group. Mild inflammatory changes and mild TNF-α expression were observed in all three treatment groups. CONCLUSION: Both hesperidin and thymol were effective in suppressing allergic symptoms and inflammation in the treatment of allergic rhinitis.